APQR is an acronym for Annual Product Quality Review. It is a regulatory requirement under which pharmaceutical companies are expected to conduct yearly product quality reviews of their commercialized products.
The purpose of APQR is as follows:
- To demonstrate the capability of the manufacturing process to consistently meet product quality specifications.
- To assess the yearly trends in product quality.
- To assess the need for changes in specifications.
- To assess the need for changes in the production line.
- To assess the need for changes in the manufacturing process.
- To assess the need for changes in control procedures.
- To assess the need for product or process revalidation.
APQR ensures that manufacturers’ responsibility for managing product quality extends beyond obtaining product approval for commercialization. Therefore, much like any other pharmaceutical regulatory requisite, the ultimate goal of the APQR is to keep a check on the product quality specification by adding another layer of review mechanism. Thereby ensuring the long-term safety and efficacy of the commercialized products.
APQR Guidelines/Regulations
According to 21 CFR 211.180 (e), drug product manufacturing companies must evaluate written records for quality standards of each drug product at least once annually. The records must be evaluated to determine the need for the change in the drug product specification, manufacturing, or control procedures.
The manufacturers must review a representative number of batches, whether approved or rejected, and, where applicable, records associated with the batch. Additionally, manufacturers must review complaints, recalls, returned or salvaged drug products, and investigations conducted under 21 CF 211.192 for each drug product.
In its APQR the PIC/S APQR guidelines require starting and packing material critical in-process controls, failed batch and their investigation, deviations and changes carried out in the process, and analytical procedure.
CH Q7 states that Quality Product Review should be conducted annually and the reason for the corrective action should be documented and completed in time.
When should you submit the APQR
APQR must cover a one-year rolling period that may be different from the calendar year. In addition to a year, manufacturers also get an extendable timeline of 3 months (60 days). Therefore, you must ensure to submit APQR by the end of the first quarter after the product anniversary.
Who is responsible for the APQR compliance?
The APQR compliance is the primary responsibility of the Quality Assurance Department on behalf of the manufacturer. The QA should create a Standard Operating Procedure outlining purpose, roles and responsibilities, and clear-cut procedures for meeting APQR compliance requirements. QA can collaborate with other business functions such as regulatory affairs, production, engineering, manufacturing sciences, and technology to garner the necessary information. All these business functions collaborate to prepare a comprehensive APQR report with inputs from all the stakeholders. The report must be finally reviewed by a senior Quality Assurance person before it is submitted to the concerned regulatory agency.
Why is the APQR important?
The manufacturer has several benefits of complying with the APQR requirements as follows:
- It identifies potential failure areas in the future and prevents expenses on investigating an out-of-specification result.
- It is a proactive approach that can be leveraged by the manufacturers to reduce rework.
- It decreases the downtime in manufacturing by actively monitoring the control procedures.
- It increases productivity by developing a better understanding of the manufacturing processes.
- It decreases the risk of product recalls.
- It prevents damage to the manufacturer’s reputation by reducing the chances of product recalls.
The deeper product and process understanding empowers the manufacturer to consistently meet regulatory commitments in terms of product quality.
Additionally, it improves communication between different business functions including but not limited to regulatory affairs, quality assurance, engineering, and production.
How to meet important requisites to meet the APQR?
The first and most important step of APQR compliance is to collect data/information for the APQR report. The second step is to review the data/information, and the third and final step is to compile a report based on the collected and reviewed data/information. Below are some important tips to complete all the three steps mentioned above successfully:
Data Collection
Collect data for all batches manufactured in the last year. Ensure to collect data for all the markets where the product is sold. Collect data for all strengths and all packs that are manufactured.
Data Review
In case the product is being manufactured in multiple strengths and different packs, then a combined report can be generated. However, each strength or packs need to be evaluated separately.
For products with more than 15 batches, it is mandatory to submit graphical data showing trends of in-process and finished products. In case the manufactured batches of a product do not exceed 15, then a trend of minimum/maximum values for in-process and finished products can be submitted. Companies should maintain an APQR tracking register.
APQR Report
The APQR report should mention the product name, year, and unique APQR number, along with the name of the manufacturer. The data/information in APQR can be represented with the help of tables, graphs, flow charts, appropriate statistics, etc. Below is an example of an outline of an APQR Report:
- Objective
- Introduction
- Product details
- Process flow
- Review of manufacturing-related information
- Batch
- Stagewise yield
- Rejections
- Reworking
- Review of critical quality parameters
- In-process and intermediate testing results
- Review of finished product testing results
- Out of specification
- Review of:
- Events
- Changes
- Market complaints
- Control samples
- Recall and returns
- Stability data
- Validation and qualification status
- Post-marketing commitments
- Quality of APIs, key raw materials, and key packing materials
- Technical agreement
- Statistical evaluation of the data
- Review of status against previous APQR
- Conclusion
- Recommendations
- Abbreviations
- Annexures
- Approval
Conclusion
In conclusion, the Annual Product Quality Review (APQR) is a regulatory requirement for pharmaceutical companies to conduct yearly product quality reviews of their commercialized products. The primary responsibility of APQR compliance lies with the Quality Assurance Department. The QA department should collaborate with other business functions to prepare a comprehensive APQR report. By complying with APQR requirements, manufacturers can identify potential failure areas, reduce rework, increase productivity, decrease downtime, prevent product recalls, and improve communication between different business functions. APQR ensures the long-term safety and efficacy of the commercialized products and helps to maintain the manufacturer’s reputation. Therefore, pharmaceutical companies need to meet the APQR requirements to ensure the quality of their products and comply with regulatory standards.
